Abstract:
Acute pancreatitis is an inflammatory disorder of the pancreas. Most progress in research of its pathogenesis was obtained
from experimental models in rats and mice. In the initial onset, trypsinogen activation plays a critical role. Proteomic studies of exocrine pancreatic tissue revealed differences in trypsinogen isoform patterns of various mouse strains. In the present study, we asked what is the extent of trypsinogen activation, if any, in caerulein-hyperstimulated pancreatic acini prepared from four different mouse strains. The strains used were CD1 and NMRI, which are vigorously outbred, and C57BL/6 and FVB, which are inbred. The pancreatic acini were isolated from the pancreata using collagenase digestion. Acini were stimulated with 0.1µM caerulein. Trypsin activity was fluorometrically measured with the fluorogenic substrate BZiPAR
(Molecular Probes/USA). Protein concentration in acini homogenates was estimated by Bradford. Cell injury in acini suspensions was quantified based on measurement of lactate dehydrogenase (LDH) activity with the Cytotoxicity Detection
Kit (Roche/Germany). C57BL/6 showed four to five times higher trypsin activation than the other three strains, although
initial trypsinogen content was not statistically different. Cell injury measured by LDH release, does not correlate with the levels of trypsin activity. Higher trypsin activity in caerulein hyperstimulated acini of C57BL/6 is accompanied by an increased Cathepsin B activitiy. Different levels of trypsinogen activation in various strains might be caused by different quantities of various trypsinogen isoforms in mouse strains, different activities of trypsinogen-activation enzymes (such as
Cathepsin B), and/or various levels of trypsin inhibitors. Future studies will focus on these questions.
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